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2,4-Dichlorophenoxyacetic acid

Names
IUPAC name (2,4-Dichlorophenoxy)acetic acid
Other names 2,4-D hedonal trinoxol 2',6'-Diethyl-N-butoxymethyl-2-chloroacetanilide
Identifiers
CAS Number	94-75-7
3D model (JSmol)	Interactive image
ChEBI	CHEBI:28854
ChEMBL	ChEMBL367623
ChemSpider	1441
ECHA InfoCard	100.002.147
KEGG	C03664
PubChem CID	1486
UNII	2577AQ9262
CompTox Dashboard (EPA)	STEM
InChI InChI=1S/C8H6Cl2O3/c9-5-1-2-7(6(10)3-5)13-4-8(11)12/h1-3H,4H2,(H,11,12)Key: OVSKIKFHRZPJSS-UHFFFAOYSA-N InChI=1/C8H6Cl2O3/c9-5-1-2-7(6(10)3-5)13-4-8(11)12/h1-3H,4H2,(H,11,12)Key: OVSKIKFHRZPJSS-UHFFFAOYAM
SMILES Clc1cc(Cl)ccc1OCC(=O)O
Properties
Chemical formula	C8H6Cl2O3
Molar mass	221.04 g/mol
Appearance	white to yellow powder
Melting point	140.5 °C (284.9 °F; 413.6 K)
Boiling point	160 °C (320 °F; 433 K)
Solubility in water	900 mg/L
Hazards
Flash point	nonflammable
Lethal dose or concentration (LD, LC):
LD50 (median dose)	500 mg/kg (oral, hamster) 100 mg/kg (oral, dog) 347 mg/kg (oral, mouse) 699 mg/kg (oral, rat)
NIOSH (US health exposure limits):
PEL (Permissible)	TWA 10 mg/m
REL (Recommended)	TWA 10 mg/m
IDLH (Immediate danger)	100 mg/m
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). N verify (what is  ?) Infobox references

2,4-Dichlorophenoxyacetic acid (usually referred to by its abbreviation, 2,4-D) is a common systemic herbicide used in the control of broadleaf weeds. It is one of the most widely used herbicides in the world. 2,4-D is a synthetic auxin (plant hormone), and as such it is often used in laboratories for plant research and as a supplement in plant cell culture media such as MS medium.

2,4-D was one of the ingredients in Agent Orange, the herbicide widely used during the Vietnam war. According to the US National Pesticide Information Center, "the controversy regarding health effects centered around the 2,4,5-T component of the herbicide and its contaminant, dioxin."

History

2,4-D was first published by Robert Pokorny in 1941, who was working in the US; the related compound, MCPA, was discovered at about the same time by scientists in UK. Both compounds were developed afterwards as part of a clandestine wartime effort to create chemical warfare agents for use in World War II; 2,4-D was not used this way in WWII.

The first publication of 2,4-D's herbicidal activity came in 1944.

2,4-D was brought to market as an herbicide called "Weedone" starting in 1945 by the American Chemical Paint Company. It revolutionized weed control, as it was the first compound that, at low doses, could selectively control dicots (broadleaf plants), but not most monocots - narrow leaf crops like wheat, maize (corn), rice, and similar cereal grass crops. At a time when labor was scarce and there was a huge need for increased food production, it literally "replaced the hoe".

2,4-D was one of the ingredients in Agent Orange, the herbicide widely used during the Vietnam war. According to the US National Pesticide Information Center, "the controversy regarding health effects centered around the 2,4,5-T component of the herbicide and its contaminant, dioxin."

In the 2000s Dow Agrosciences developed a new choline salt version of 2,4-D (2,4-D choline) that Dow included in its "Enlist Duo" herbicide along with glyphosate and an agent that reduces drift; the choline salt form of 2,4-D is less volatile than 2,4-D.

Mode of action

2,4-D is a synthetic auxin, which is a class of plant hormones. It is absorbed through the leaves and is translocated to the meristems of the plant. Uncontrolled, unsustainable growth ensues, causing stem curl-over, leaf withering, and eventual plant death. 2,4-D is typically applied as an amine salt, but more potent ester versions exist as well.

Manufacture

2,4-D is a member of the phenoxy family of herbicides.

2,4-D is manufactured from chloroacetic acid and 2,4-dichlorophenol, which is itself produced by chlorination of phenol. Alternatively, it may be produced by the chlorination of phenoxyacetic acid. The production processes create several contaminants including di-, tri-, and tetrachlorodibenzo-p-dioxin isomers and N-nitrosamines, as well as monochlorophenol.

Applications

2,4-D is primarily used as a synthetic auxin analog, as an herbicide. It is sold in various formulations under a wide variety of brand names. 2,4-D can be found in commercial lawn herbicide mixtures. These products often contain other active ingredients including mecoprop and dicamba. Over 1,500 herbicide products contain 2,4-D as an active ingredient.

2,4-D is most commonly used for weed control in lawns and other turf and control of weeds and brush along fences and highway and railroad rights of way. In agriculture it is used as a soil application in orchards, while foliar application is used in grass hayfields, pastures, cereal grains, including corn and sorghum (occasionally).

2,4-D continues to be used, where legal, for its low cost. Where municipal lawn pesticide bylaws exist, such as in Canada, alternatives must be used.

A 2010 monitoring study conducted in the US and Canada found that "current exposures to 2,4-D are below applicable exposure guidance values."

Toxicity

According to a FAQ published by the U.S. Environmental Protection Agency: "2,4-D products can be safely used by following label directions. The toxicity of 2,4-D depends on its chemical forms, including salts, esters, and an acid form. 2,4-D generally has low toxicity for humans, except certain acid and salt forms can cause eye irritation. Swimming is restricted for 24 hours after application of certain 2,4-D products applied to control aquatic weeds to avoid eye irritation. 2,4-D generally has moderate toxicity to birds and mammals, is slightly toxic to fish and aquatic invertebrates, and is practically nontoxic to honeybees. The ester forms of 2,4-D can be highly toxic to fish and other aquatic life. Carefully follow label directions to avoid harmful effects."

2,4-D has been shown to negatively affect male fertility.

Metabolism

When radioactively labeled 2,4 D was fed to livestock, 90% or more of the total radioactive residue (TRR) was shed in urine unchanged or as conjugated forms of 2,4-D. A relatively small portion of 2,4 D was metabolized into dichlorophenol and into dichloroanisole and 4-chlorophenoxyacetic acid. (6.9% of the TRR in milk) and 2,4-dichlorophenol13 (5% of the TRR in milk; 7.3% of the TRR in eggs and 4% of the TRR in chicken liver). Residue levels in kidney were the highest.

Acute toxicity

As of 2005 the Median lethal dose or LD₅₀ determined in acute toxicity rat studies was 639 mg/kg.

While urinary alkalinisation has been used in acute poisonings, evidence to support its use is poor.

Contaminants

It was assumed that because of improved manufacturing processes that there were no longer any dangerous dioxins in 2,4-D; however, a July 2013 Four Corners investigation found elevated levels of dioxins in a generic version of 2,4-D, which is one of Australia's most widely used herbicides. One scientist said the product tested by Four Corners, which was imported from China, had "one of the highest dioxin readings for 2,4-D in the last 10 to 20 years, and could pose potential health risks."

Cancer risk

On August 8, 2007, the EPA issued a ruling that existing data do not support a link between human cancer and 2,4-D exposure.

A 1995 panel of 13 scientists reviewing studies on the carcinogenicity of 2,4-D had divided opinions. None of the scientists thought the weight of the evidence indicated that 2,4-D was a “known” or “probable” cause of human cancer. The predominant opinion indicated that it is possible that 2,4-D can cause cancer in humans, although not all of the panelists believed the possibility was equally likely: one thought the possibility was strong, leaning toward probable, and five thought the possibility was remote, leaning toward unlikely. Two panelists believed it unlikely that 2,4-D can cause cancer in humans.

In a 1987 report by the International Agency for Research on Cancer (IARC) which concluded that some chlorphenoxy herbicides including 2,4-D, MCPA and 2,4,5-T as a group were classified as a class 2B carcinogen - "possibly carcinogenic to humans".

Environmental behavior

Owing to the longevity and extent of use, 2,4-D has been evaluated several times by regulators and review committees.

2,4-D amine salts and esters are not persistent under most environmental conditions. The degradation of 2,4-D is rapid (half life of 6.2 days) in aerobic mineral soils. 2,4-D is broken down by microbes in soil, in processes that involve hydroxylation, cleavage of the acid side-chain, decarboxylation, and ring opening. The ethyl hexyl form of the compound is rapidly hydrolyzed in soil and water to form the 2,4-D acid. 2,4-D has a low binding affinity in mineral soils and sediment, and in those conditions is considered intermediately to highly mobile, and therefore likely to leach if not degraded.

In aerobic aquatic environments, the half life is 15 days, while in anaerobic aquatic environments, 2,4-D was moderately persistent to persistent (half life of = 41 to 333 days). 2,4-D has been detected in streams and shallow groundwater at low concentrations, in both rural and urban areas. Breakdown is pH dependent.

Microbial breakdown

A number of 2,4-D-degrading bacteria have been isolated and characterized from a variety of environmental habitats. Metabolic pathways for the compound’s degradation have been available for many years, and genes encoding 2,4-D catabolism have been identified for several organisms. As a result of the extensive metadata on environmental behavior, physiology and genetics, 2,4-D was the first herbicide for which the bacteria actively responsible for in situ degradation was demonstrated. This was accomplished using the technique of DNA-based stable isotope probing, which enables a microbial function (activity), such as degrading a chemical, to be linked with the organism’s identity without the need to culture the organism involved.

Regulation

Maximum residue limits were first set in the EU in 2002 and re-evaluated by the European Food Safety Authority in 2011. EFSA concluded that the codex maximum residue limits were "not expected to be of concern for European consumers". The total chronic exposure represented less than 10% of the acceptable daily intake (ADI). Concern over 2,4-D is such that it is currently not approved for use on lawns and gardens in Denmark, Norway, Kuwait and the Canadian provinces of Québec and Ontario. 2,4-D use is severely restricted in the country of Belize.

In 2005, the US EPA approved the continued use of 2,4-D. On July 10, 2013 the Pest Management Regulatory Agency in Canada updated the re-evaluation notice of 2,4-D stating that the 2,4-D registrants had provided it with required data and deemed them acceptable. On April 18, 2012, EPA denied the petition filed November 6, 2008 by the Natural Resources Defense Council (NRDC) to revoke all tolerances and to cancel all registrations of 2,4-D. EPA stated that recent new study and EPA’s comprehensive review confirmed EPA’s previous finding that the 2,4-D tolerances are safe at anticipated exposure.

In October 2014, the US EPA registered Enlist Duo herbicide containing the less volatile 2,4-D choline salt, glyphosate, and an anti-drift agent, for use in six states: Illinois, Indiana, Iowa, Ohio, South Dakota, and Wisconsin.

On 21 August 2013 the Australian Pesticides and Veterinary Medicines Authority (APVMA) banned selected 2,4-D high volatile ester (HVE) products due to their environmental hazards. HVE 2, 4-D products had already been banned in Europe and North America for twenty years; low volatile ester products continue to be available in Australia and worldwide. In July 2013 APVMA published their report findings.

Genetically modified crops

In 2010 Dow published that it had created genetically modified soybeans made resistant to 2,4-D by insertion of a bacterial aryloxyalkanoate dioxygenase gene, aad1. Dow intended it to be used as an alternative or complement to Roundup Ready crops due to the increasing prevalence of glyphosate resistant weeds.

As of April 2014 maize and soybeans resistant to 2,4-D and glyphosate have been approved in Canada. In September 2014 the USDA approved Dow's soybeans and maize and in October the EPA registered the "Enlist Duo" herbicide containing 2, 4-D and glyphosate.

See also

• Genetically modified crops#Herbicide resistance
• Genetic pollution

References

1. "ChemIndustry site". Chemindustry.com. Retrieved 2014-05-03.
2. ^ NIOSH Pocket Guide to Chemical Hazards. "#0173". National Institute for Occupational Safety and Health (NIOSH).
3. "2,4-D". National Institute for Occupational Safety and Health. 4 December 2014. Retrieved 26 February 2015.
4. ^ National Pesticide Information Center NPIC 2,4-D Technical Fact Sheet
5. ^ Andrew H. Cobb, John P. H. Reade. Herbicides and Plant Physiology. Wiley-Blackwell; 2nd edition (October 25, 2010) ISBN 978-1405129350
6. Robert Pokorny New Compounds. Some Chlorophenoxyacetic Acids J. Am. Chem. Soc., 1941, 63 (6), pp 1768–1768 doi:10.1021/ja01851a601
7. J. H. Quastel. 2,4-dichlorophenoxyacetic acid (2,4-D) as a selective herbicide. Chapter 45 (pp 244-249) in Advances in Chemistry, Vol. 1: Agricultural Control Chemicals: Collected Papers from the Symposia on Economic Poisons presented before the Division of Agricultural and Food Chemistry of the American Chemical Society at the 115th national meeting in San Francisco, March 28 to April 1, 1949, and the 116th national meeting in Atlantic City, September 18 to 23, 1949. American Chemical Society, 1950. Washington, D.C. ISBN 9780841224421
8. Hamner CL, Tukey HB (1944). "The Herbicidal Action of 2,4 Dichlorophenoxyacetic and 2,4,5 Trichlorophenoxyacetic Acid on Bindweed" (PDF). Science. 100 (2590): 154–155. doi:10.1126/science.100.2590.154. PMID 17778584.
9. PAN Pesticides Database. 2,4-D, choline salt Page accessed April 24, 2015
10. ^ Donna Fleury (April 2014). "Enlist weed control system in Canada. A new tool for managing hard to control and resistant weeds". AG Annex. Retrieved May 3, 2014.
11. Josh Flint for Prairie Farmer. August 31, 2011 Dow AgroSciences Names Its Newest Herbicide Offering Enlist Duo
12. ^ EPA Press Release. October 15, 2014 EPA Announces Final Decision to Register Enlist Duo, Herbicide Containing 2, 4-D and Glyphosate/Risk assessment ensures protection of human health, including infants, children EPA Documents: Registration of Enlist Duo
13. Song Y. Insight into the mode of action of 2,4-dichlorophenoxyacetic acid (2,4-D) as an herbicide. J Integr Plant Biol. 2014 Feb;56(2):106-13. doi: 10.1111/jipb.12131. PMID 24237670
14. International Programme on Chemical Safety (1984). "2,4-Dichlorophenoxyacetic Acid (2,4-D)". UNEP, WHO ILO. Retrieved 22 June 2010.
15. Template:HPD
16. EPA Last revised March 30, 2007 EPA Chemical Summary: 2,4-Dichlorophenoxyacetic Acid (2,4-D)
17. ^ European Food Safety Authority. Reasoned opinion of EFSA: Review of the existing maximum residue levels (MRLs) for 2,4-D according to Article 12 of Regulation (EC) No 396/2005 EFSA Journal 2011;9(11):2431.1-52 doi:10.2903/j.efsa.2011.2431
18. "Private Property Pesticide By-laws In Canada" (PDF). flora.org. n.d. Retrieved 2014-05-03.
19. Aylward LL et al. Biomonitoring data for 2,4-dichlorophenoxyacetic acid in the United States and Canada: interpretation in a public health risk assessment context using Biomonitoring Equivalents. Environ Health Perspect. 2010 Feb;118(2):177-81. doi: 10.1289/ehp.0900970. PMCID PMC2831914 PMID 20123603 url=?
20. "Ingredients Used in Pesticide Products 2,4-D". www2.epa.gov. EPA. Retrieved November 6, 2014.
21. Harley, Kim G.; Marks, Amy R.; Bradman, Asa; Barr, Dana B.; Eskenazi, Brenda (Dec 2008). "DDT exposure, work in agriculture, and time to pregnancy among farmworkers in California". Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 50 (12): 1335–1342. doi:10.1097/JOM.0b013e31818f684d. ISSN 1536-5948. PMC 2684791. PMID 19092487.
22. ^ US EPA 2,4-D Reregistration Eligibility Decision, 2005. Associated RED Fact sheet
23. Roberts DM, Buckley NA (2007). Roberts, Darren M (ed.). "Urinary alkalinisation for acute chlorophenoxy herbicide poisoning". Cochrane Database Syst Rev (1): CD005488. doi:10.1002/14651858.CD005488.pub2. PMID 17253558.
24. Four Corners By Janine Cohen (22 July 2013). "Four Corners investigation finds dangerous dioxins in widely used herbicide 24D". Abc.net.au. Retrieved 2014-05-03.
25. "EPA: Federal Register: 2,4-D, 2,4-DP, and 2,4-DB; Decision Not to Initiate Special Review". Epa.gov. August 8, 2007. Retrieved 2014-05-03.
26. Ibrahim, MA; Bond, GG; Burke, TA; Cole, P; Dost, FN; Enterline, PE; et al. (1991). "Weight of the evidence on the human carcinogenicity of 2,4-D". Environ Health Perspect. 96: 213–22. doi:10.1289/ehp.9196213. PMC 1568222. PMID 1820267.
27. Chlorphenoxy Herbicides (Group 2B) in IARC monographs on the evaluation of carcinogenic risks to humans: An updating of IARC Monographs volumes 1 to 42. Supplement 7, WHO, Lyon, France 1987.
28. von Stackelberg K. A (2013). "Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment". J Toxicol. 2013: 371610. doi:10.1155/2013/371610. PMID 23533401.{{cite journal}}: CS1 maint: unflagged free DOI (link)
29. ^ Andrew Pollack for the New York Times. April 9, 2012 E.P.A. Denies an Environmental Group’s Request to Ban a Widely Used Weed Killer Quote: "The E.P.A. has reviewed the safety of 2,4-D several times, particularly with regard to an increased risk of cancer."
30. Cavalca, L., A. Hartmann, N. Rouard, and G. Soulas. 1999. Diversity of tfdC genes: distribution and polymorphism among 2,4-dichlorophenoxyacetic acid degrading soil bacteria. FEMS Microbiology Ecology 29: 45-58.
31. Suwa Y., Wright A.D., Fukimori F., Nummy K.A., Hausinger R.P., Holben W.E., Forney L.J. (1996). "Characterization of a chromosomally encoded 2,4-dichlorophenoxyacetic acid alpha-ketoglutafate dioxygenase from Burkholderia sp. strain RASC". Applied and Environmental Microbiology. 62: 2464–2469.{{cite journal}}: CS1 maint: multiple names: authors list (link)
32. Cupples A.M., Sims G.K. (2007). "Identification of In Situ 2,4-Dichlorophenoxyacetic Acid-Degrading Soil Microorganisms using DNA-Stable Isotope Probing". Soil Biology and Biochemistry. 39: 232–238. doi:10.1016/j.soilbio.2006.07.011.
33. Radajewski S., Ineson P., Parekh N.R., Murrell J.C. (2000). "Stable-isotope probing as a tool in microbial ecology". Nature. 403: 646–649. doi:10.1038/35001054.{{cite journal}}: CS1 maint: multiple names: authors list (link)
34. "The Pesticides Management Code - Protecting the environment and health in our green spaces". Mddep.gouv.qc.ca. 2005-04-03. Retrieved 2014-05-03.
35. "Ministry of the Environment | Ontario.ca". Ene.gov.on.ca. Retrieved 2014-05-03.
36. "Health Canada Pest Management Regulatory Agency Re-evaluation Update 2,4-D REV2013-02". Hc-sc.gc.ca. Retrieved 2014-05-03.
37. "Petition to Revoke All Tolerances and Cancel All Registrations for the Pesticide 2,4-Dichlorophenoxyacetic Acid (2,4-D); Notice of Availability" (Docket Folder Summary). Docket ID: EPA-HQ-OPP-2008-0877 Agency: EPA. United States Environmental Protection Agency. April 7, 2012. Retrieved September 12, 2012.
38. "2,4-D; Order Denying NRDC's Petition To Revoke Tolerances" (Order). Federal Register. 77 (75 (Wednesday, April 18, 2012)): 23135–23158. April 18, 2012. Retrieved September 12, 2012. Petitions to Revoke Tolerances; Denials: Natural Resources Defense Council, 2,4-dichlorophenoxyacetic acid (2-4D) Document ID: EPA-HQ-OPP-2008-0877-0446 Document Type: Rule Docket ID: EPA-HQ-OPP-2008-0877
39. "APVMA 2,4-D Review webpage". APVMA.
40. "Annex to the APVMA's Preliminary Review Findings (Environment) Part 1 2,4-D Esters Volume 1 Review Summary April 2006" (PDF). APVMA. July 2013. Retrieved July 2014. {{cite web}}: Check date values in: |accessdate= (help)
41. Wright TR et al. Robust crop resistance to broadleaf and grass herbicides provided by aryloxyalkanoate dioxygenase transgenes. Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20240-5. doi 10.1073/pnas.1013154107 PMCID 2996712 PMID 21059954
42. ^ ISAAA GM Approval Database GM Approval Database Genes List, Gene: aad1. International Service for the Acquisition of Agri-biotech Applications (ISAAA), n.d. accessed February 27, 2015
43. Mark A. Peterson, Guomin Shan, Terence A. Walsh, and Terry R. Wright. Utility of Aryloxyalkanoate Dioxygenase Transgenes for Development of New Herbicide Resistant Crop Technologies ISB News Report,3 pages, May 2011, Research & Development, Dow AgroSciences, Indianapolis
44. Andrew Pollack (April 25, 2012). "Dow Weed Killer, Nearing Approval, Runs Into Opposition". The New York Times. Retrieved April 25, 2012.
45. Brandon Keim (25 September 2014). "New Generation of GM Crops Puts Agriculture in a 'Crisis Situation'". Wired. Condé Nast. Retrieved 13 April 2015.

External links and further reading

• CDC - NIOSH Pocket Guide to Chemical Hazards
• Overview of the toxic effects of 2,4-D Sierra Club Canada January, 2005
• "Review of 2,4-dichlorophenoxyacetic acid (2,4-D) biomonitoring and epidemiology" Review of the literature by Dow scientists Crit Rev Toxicol. Oct 2012

• Chloroarenes
• Auxinic herbicides
• Phenol ethers
• Acetic acids